34 results about "Specific immune cell" patented technology

The present invention relates to expression of RORγt in cells and tissues and the effect of expression of this gene on proliferation of specific immune cells and in promotion of immune cell aggregates and in induction of IL17 producing cells. Furthermore, the invention relates to methods and agents that may decrease function of the gene product (the protein) or expression of this gene in individuals experiencing an inflammatory condition, an autoimmune disease or a food allergy, or any other condition whereby it is desirable to inhibit an immune response. In addition, methods and agents useful for enhancing the function of RORγt with agonists or expression of this gene are also considered for use whereby it is desirable to increase immunity to a pathogen or tumor cell, for example, for use in conjunction with a vaccine. Screening methods for identifying novel modulators (antagonists and agonists) of RORγt are also disclosed.

A method of treating a malignant solid tumor in a subject is disclosed herein. The method includes the steps of administering to the subject an immunomodulatory dose of a radiohalogenated compound that is differentially taken up by and retained within malignant solid tumor tissue, and performing in situ tumor vaccination in the subject by intratumorally injecting into (or treating via a separate method) at least one of the malignant solid tumors a composition that includes one or more agents capable of stimulating specific immune cells within the tumor microenvironment. In certain exemplary embodiments, the radiohalogenated compound has the formula:wherein R1 is a radioactive halogen isotope, n is 18 and R2 is —N+(CH3)3.

The present invention provides (poly)peptides, which are recognized by human cytomegalovirus (CMV)-specific immune cells. The present invention further provides a combination of multiple CMV (poly)peptides, comprising at least two different groups of (poly)peptides according to the invention as well as conjugates, comprising said (poly)peptides and / or immune adjuvants thereof. Furthermore, this invention provides mixtures, comprising said (poly)peptides and / or immune cells thereof, which are used to generate CMV-specific immune effector cells with high sensitivity and specificity. In addition, the present invention provides a preparation method of CMV-specific immune effector cells, by using said (poly)peptides, adjuvants, immune cells and / or mixtures thereof to generate anti-CMV immune response.

It has been discovered that HLA-G dimers are potent ligands of ILT2 and ILT4 on immune cells and enhance signal transduction through ILT2 and ILT4. Enhanced signal transduction through ILT-2, ILT-4 or both down-regulates the biological activity of T cells and dendritic cells. HLA-G compositions including HLA-G dimers are provided that are useful for modulating activity of immune cells. Preferred compositions include microparticles having HLA-G dimers on the surface of the microparticles. The microparticles optionally include a targeting moiety to target the microparticles to specific immune cells. In a preferred embodiment the microparticles are targeted to T cells or dendritic cells expressing ILT2 or both ILT2 and ILT4, respectively. The HLA-G dimer can include any HLA-G protein that is capable of forming a dimer. Preferred HLA-G proteins include HLA-G1 and HLA-G5. In certain embodiments the microparticles include dimers of HLA-G1 and HLA-G5.

The invention provides a preparation method of a body immune function-enhancing biological drug. The method includes: step 1. subjecting an immune cell and a specific antigen to co-culture in a liquid cell medium, which comprises a cell mitogen, an antigen, a super antigen, a cell factor, and an immune adjuvant, etc., thus obtaining a specific immune cell culture resisting the corresponding antigen; and step 2. separating a cell with an immune response from the culture obtained in step 1. The biological preparation and drug prepared in the invention have good safety, high activity, and can effectively improve the body immune function, thus being able to be used in treatment and prevention of malignant tumors, virus infections (such as acquired immune deficiency syndrome and hepatitis) and other immune function related diseases.

The invention belongs to the field of medical biotechnology, and particularly relates to a genetically modified immune cell with a malignant solid tumor treating function and application thereof. The immune cell is a specific immune cell which is subjected to gene modification so as to over-express lipid metabolism-related genes. The tumor growth inhibiting capacity of the immune cell is realized by reducing accumulation of lipid droplets of the immune cell itself in a tumor microenvironment, reducing expression of tumor promotion genes / protein, and improving the phagocytotic ability, antigen presentation ability and tumor killing ability of the immune cell. The immune cell is an in-vitro NKT cell, a DC cell, a macrophage, a monocyte, a granulocyte or a T cell. Overexpression of related metabolism regulation genes enables the anti-tumor capacity of the immune cell to be improved remarkably. Compared with a chimeric antigen receptor T cell immunotherapy (CAR-T) which receives much attention currently, toxic and side effects are small, cytokine storm can not be caused, and clinical requirements can be met.

The present invention relates to pseudotyped retrovirus-like particles or retroviral vectors comprising both engineered envelope glycoproteins derived from a virus of the Paramyxoviridae family fusedto a cell targeting domain and fused to a functional domain. The present invention also relates to the use of said pseudotyped retrovirus-like particles or retroviral vectors to selectively modulate the activity of specific subsets of cells, in particular of specific immune cells. These pseudotyped retrovirus-like particles or retroviral vectors are particularly useful for gene therapy, immune therapy and / or vaccination.

The invention provides a cell biological drug and a biological preparation for allogeneic adoptive cellular immunotherapy of blood system diseases such as MDS (myelodysplastic syndromes) or leukemia, and a preparation method. The preparation method of the cell biological drug consists of: subjecting an immune cell and an antigen to co-culture in a liquid cell culture medium in a culture container so as to obtain a specific immune cell culture resisting the corresponding antigen; and separating a cell biological drug with an immune response from the obtained culture. The immune cell can be an allogeneic cell, has no allogeneic rejection reaction in use, and has high security. After treatment of MDS, hematopoietic functions in bone marrow puncture, bone marrow biopsy and bone marrow stem cell culture are all significantly improved. In a treatment process, patients have good tolerance. In the invention, MDS is treated by means of a brand new etiological treatment strategy of improving organism immunity, and the hematopoietic function in patients is effectively restored. The cell biological drug provided in the invention has good prospects for treatment of other hematopoietic stem cell malignant cloning diseases including leukemia.

The invention discloses a method for amplifying and multiplying T cells with antigenic specificity, which comprises the following steps of: stimulating the T cells by using an immunogen A to obtain the T cells with the immunogen A specificity aiming at a polypeptide-MHC molecular compound of the immunogen A; transferring a coding gene of an immunological identification molecule for recognizing a polypeptide-MHC molecular compound of a target antigen B into the T cells with the immunogen A specificity to obtain the T cells with bi-anti-specificity for recognizing the polypeptide-MHC molecular compound of the target antigen B and the polypeptide-MHC molecular compound of the immunogen A; and stimulating to amplify and multiply the T cells with bi-anti-specificity by using the immunogen A. The T cells with bi-anti-specificity prepared by the method simultaneously have the target antigen B specificity and the immunogen A specificity; the induction and expanding culture are performed by using the immunogen A so as to obtain a great number of immune cells with the target antigen B specificity; the defect that the conventional antigen with weak immunogenicity cannot induce the specific immune cells to multiply in vitro is overcome; and the multiplied T cells with the bi-anti-specificity have high kill rate for the target antigen.

The invention discloses a tumor infiltrating lymphocyte analysis method and device and a storage medium, and the method comprises the steps of obtaining a pathological image of a to-be-detected tumor tissue slice, the pathological image being a multiple immunohistochemical staining image or a multiple immunofluorescent staining image; identifying phenotypes of different cells according to the target marker expression signal of the pathological image so as to obtain cell phenotype data corresponding to the target marker; and performing quantitative and / or qualitative analysis on the tumor infiltrating lymphocytes according to the cell phenotype data corresponding to the target marker. According to the tumor infiltrating lymphocyte analysis method, TILs subgroups are deeply analyzed through mIHC / IF detection, specific immune cell types can be analyzed, the relation between immune cells of different parts of a tumor can be integrated, more immunotherapy prognosis data and prediction data are obtained, and the problem that tumor immunotherapy curative effect evaluation is lack of biomarkers is solved.

The invention relates to identification of specific immune cell subtypes in new coronavirus infected peripheral blood and application of the specific immune cell subtypes, and provides immune cell populations and subpopulations which play an important role in occurrence and development of COVID-19 diseases. The first class can be used for T cell immunotherapy, DC cell immunotherapy and B cell immunotherapy of new coronal pneumonia and immunotherapy of old patients; the second class can be used for screening and designing a medicine for inhibiting cytokine storm and a medicine for inhibiting T cell reduction; the third class can be used for diagnosis of new coronal pneumonia.

This invention is related to a peptides mixture. Without the need to consider the patients' genetic background, it can interfere with MHC-pathogenic peptide-TCR formation, which includes the interference with pathogen peptide binding with MHC and pMHC binding with specific TCR, suppression of the immune synapse formation when the specific T cell immune response occurs, reduction of the number and density of the MHC-specific immune response mediated pathogenic peptide-TCR in the immune synapse, and suppression of the highly activated signal transduction in the immune synapse. Hence it can negatively regulate the T cell specific immune response, reduce the specific immune cell activation, proliferation and effect, and make the radical T cell specific immune response more stable and last longer. It can be used to treat diseases with excessive T cell-specific immune reaction, such as severe flu, SARS, hand-foot-and-mouth disease, viral pneumonia, bacterial infections, severe autoimmune disease and etc.

The invention provides a method for cultivating and separating tumor-specific TIL cells. The method comprises the following steps: step 1, obtaining tumor cell clusters and immune cell sap in pleuroperitoneal fluids; step 2, performing tumor organoid culture on the tumor cell clusters; step 3, performing amplification culture on immune cells; step 4, treating tumor organoid obtained by culture into single cells, and co-culturing the single cells and the immune cells subjected to amplification culture; and step 5, separating a specific immune cell population in the co-cultured cells. According to the method disclosed by the invention, tumor organoids and the tumor-related immune cells are simultaneously separated and cultured by utilizing the sample from the same source, and then the tumor organoids and the immune cells are co-cultured, so that the obtained tumor-specific TIL cells can keep the biological effect of the organoids, the quantity is large, and the culture period is obviously shortened. In addition, the TIL cells separated and cultured by the method are higher in tumor specificity, so that the tumor killing activity is higher.

A system for inducing activity of immune cells comprising a chimeric antigen receptor, a T cell receptor, and various combinations thereof, an isolated host cell expressing the system, an antigen-specific immune cell comprising the system and methods of immunotherapy are provided.

A highly specific and beneficial T cell therapy can be provided by controlled ex vivo induction or amplification to produce antigen-specific immune cells (like T cells). The invention provides T cell manufacturing methods and therapeutic T cell compositions, for example, for treating subjects with cancer and other conditions, diseases and disorders, as well as individual antigen-specific T cell therapies.

In accordance with an embodiment of the invention, there is provided a method for: a) high-throughput, multiplexed, affinity-based separation of proteins—especially low abundance proteins—from complex biological mixtures such as serum; and b) high-throughput, multiplexed, affinity-based separation of cells—especially rare cells—from complex biological mixtures such as blood or blood fractions. The separation of proteins or cells is achieved based on differential binding to affinity-capture beads of different sizes and then sorting the protein-bound or cell-bound beads using the concept of centrifugal-induced Dean migration in a spiral microfluidic device. This method enables continuous-flow, high throughput affinity-separation of milligram-scale protein samples or millions of cells in minutes after binding. This is particularly applicable to the isolation of antigen-specific antibodies from polyclonal sera and antigen-specific immune cells or circulating tumor cells from blood, both of which are otherwise highly labor-intensive and expensive to perform.

Provided herein are tumor-antigen VCX / Y specific peptides and engineered VCX / Y specific T cell receptors. Also provided herein are methods of generating VCX / Y-specific immune cells and their use for the treatment of cancer. In addition, the VCX / Y-specific peptides may be used as a vaccine.

The present invention provides modified antigen-specific immune cells expressing an exogenous CD 160 protein. In some embodiments, the modified antigen-specific immune cell further comprises a functional exogenous receptor, such as an engineered TCR or a CAR. The present invention also provides methods of modulating CD 160 activity in antigen-specific immune cells. The present invention also provides methods and pharmaceutical compositions for cancer treatment using the modified antigen-specific immune cells and the modulators of CD 160 activity described herein.

The present invention relates to expression of RORγt in cells and tissues and the effect of expression of this gene on proliferation of specific immune cells and in promotion of immune cell aggregates and in induction of IL17 producing cells. Furthermore, the invention relates to methods and agents that may decrease function of the gene product (the protein) or expression of this gene in individuals experiencing an inflammatory condition, an autoimmune disease or a food allergy, or any other condition whereby it is desirable to inhibit an immune response. In addition, methods and agents useful for enhancing the function of RORγt with agonists or expression of this gene are also considered for use whereby it is desirable to increase immunity to a pathogen or tumor cell, for example, for use in conjunction with a vaccine. Screening methods for identifying novel modulators (antagonists and agonists) of RORγt are also disclosed.

The invention provides a method for cultivating and separating tumor-specific TIL cells, comprising the following steps: step 1, obtaining tumor cell clusters and immune cell liquid in pleural and ascites; step 2, culturing tumor cell clusters in tumor organoids; step 3 , the immune cells are expanded and cultured; step 4, the tumor organoids obtained from the culture are processed into single cells and then co-cultured with the expanded and cultured immune cells; step 5: the specific immune cell population in the co-cultured cells is isolated. In the present invention, tumor organoids and tumor-related immune cells are simultaneously isolated and cultured from samples from the same source, and then tumor organoids and immune cells are co-cultured, and the obtained tumor-specific TIL cells can retain the biological effects of organoids, and the quantity Many, the cultivation period is significantly shortened. In addition, the TIL cells isolated and cultured by the method have stronger tumor specificity, and thus have stronger tumor killing activity.

The invention discloses a method for amplifying and multiplying T cells with antigenic specificity, which comprises the following steps of: stimulating the T cells by using an immunogen A to obtain the T cells with the immunogen A specificity aiming at a polypeptide-MHC molecular compound of the immunogen A; transferring a coding gene of an immunological identification molecule for recognizing a polypeptide-MHC molecular compound of a target antigen B into the T cells with the immunogen A specificity to obtain the T cells with bi-anti-specificity for recognizing the polypeptide-MHC molecular compound of the target antigen B and the polypeptide-MHC molecular compound of the immunogen A; and stimulating to amplify and multiply the T cells with bi-anti-specificity by using the immunogen A. The T cells with bi-anti-specificity prepared by the method simultaneously have the target antigen B specificity and the immunogen A specificity; the induction and expanding culture are performed by using the immunogen A so as to obtain a great number of immune cells with the target antigen B specificity; the defect that the conventional antigen with weak immunogenicity cannot induce the specific immune cells to multiply in vitro is overcome; and the multiplied T cells with the bi-anti-specificity have high kill rate for the target antigen.

The present invention relates to proteins which comprise (i) a CD25-specific binding domain, (ii) a linker domain, connecting domain (i) and domain (iii), (iii) a transmembrane domain, and (iv) a signalling domain. The present invention furthermore relates to nucleic acids encoding the proteins, expression constructs for expressing the protein in a host cell and host cells. The present invention further relates to pharmaceutical compositions comprising said protein(s), nucleic acid(s), expression construct(s) or host cell(s). The proteins of the invention are CD25-specific chimeric antigen receptors that are suitable for generating CD25-specific immune cells, which can be used e.g. in the treatment of inflammation.

The disclosed method of treating a malignant solid tumor in a subject includes the steps of administering to the subject an immunomodulatory dose of a radioactive phospholipid metal chelate compound that is differentially retained within malignant solid tumor tissue, and performing in situ tumor vaccination in the subject by introducing into at least one of the malignant solid tumors one or more agents capable of stimulating specific immune cells within the tumor microenvironment, or by performing another method of in situ tumor vaccination. In a non-limiting example, the radioactive phospholipid metal chelate compound has the formula:wherein R1 comprises a chelating agent that is chelated to a metal atom, wherein the metal atom is an alpha, beta or Auger emitting metal isotope with a half life of greater than 6 hours and less than 30 days. In one such embodiment, a is 1, n is 18, m is 0, b is 1, and R2 is —N+(CH3)3.

The present invention provides modified antigen-specific immune cells expressing an exogenous CD 160 protein. In some embodiments, the modified antigen-specific immune cell further comprises a functional exogenous receptor, such as an engineered TCR or a CAR. The present invention also provides methods of modulating CD 160 activity in antigen-specific immune cells. The present invention also provides methods and pharmaceutical compositions for cancer treatment using the modified antigen-specific immune cells and the modulators of CD 160 activity described herein.

A preparation method of composite immune cells with high killing ability to tumor cells is characterized by comprising the following steps: step 1, collecting peripheral blood, separating out mononuclear cells, culturing the separated mononuclear cells, and reserving suspension cells and adherent cells; step 2, culturing mature DC cells through the adherent cells; step 3, inoculating by using a specific immune cell basic culture solution through the suspension cells to culture a specific immune cell culture system; and step 4, adding the DC cells obtained in the step 2 into the specific immune cell culture system for co-culture.

The disclosure relates to a tumor immunotherapy composition based on specific immune cells, particularly non-integrated-antigen-peptide-plasmid-carrying attenuated-Listerella-activated specific immunecells, a preparation method and application. According to the disclosure, T cells are extracted in vitro, attenuated-Listerella-activated antigen presenting cells and the T cells are co-cultured, T cells with specific tumor antigen peptides are generated in vitro, and the specific T cells are fed back in vivo to generate tumor-specific immune reactions. According to the technical scheme disclosedby the disclosure, tumor-specific T cells can be specifically activated, and thus, a series of antitumor immune reactions are initiated; and an operating process has no need of carrying out gene reforming on autologous cells, and both targeting performance and safety are improved remarkably.

The disclosed method of treating a malignant solid tumor in a subject includes the steps of administering to the subject an immunomodulatory dose of a radioactive phospholipid metal chelate compound that is differentially retained within malignant solid tumor tissue, and performing in situ tumor vaccination in the subject by introducing into at least one of the malignant solid tumors one or more agents capable of stimulating specific immune cells within the tumor microenvironment, or by performing another method of in situ tumor vaccination. In a non-limiting example, the radioactive phospholipid metal chelate compound has the formula:wherein R1 comprises a chelating agent that is chelated to a metal atom, wherein the metal atom is an alpha, beta or Auger emitting metal isotope with a half life of greater than 6 hours and less than 30 days. In one such embodiment, a is 1, n is 18, m is 0, b is 1, and R2 is —N+(CH3)3.

The present invention relates to a method, in particular an in vitro method, for identifying specific immune cells, in particular MDSCs, comprising analyzing a modification, preferably the methylation status,of at least one CpG position in the mammalian gene region for endoplasmatic reticulum-golgi intermediate compartment 1 (ERGIC1), wherein a demethylation or lack of methylation or modification of said gene region is indicative for an MDSC, when compared to a non-MDSC. The analyses according to the invention can identify specific sub-populations of MDSCs, namely monocytic MDSCs (m MDSCs) on an epigenetic level and distinguish them from all other cells in complex samples, such as, for example, other blood or immune cells. The present invention furthermore provides an improved method for quantifying m MDSCs, in particular in complex samples. The method can be performed without a step of purifying and / or enriching cells, preferably in whole blood and / or non-trypsinized tissue.